Long before opioid abuse exploded into a public health crisis, before drugs such as OxyContin and Vicodin claimed hundreds of thousands of American lives and ruined countless others, one respected Boston University doctor had a question he wanted answered.

To find out, Hershel and his assistant, a graduate student named Jane Porter, reviewed troves of hospital records. Their conclusions were optimistic: Out of nearly 12,000 hospital patients treated with such painkillers, just four had become addicted. Only one case was considered severe. They wrote up the good news in a one-paragraph, five-sentence letter to the New England Journal of Medicine.

“We conclude,” read the letter, “that despite widespread use of narcotic drugs in hospitals, the development of addiction is rare in medical patients with no history of addiction.”

That was in January 1980. Over the following decades, the letter was invoked by doctors, academics, pharmaceutical companies and others as evidence that few users would develop addictions and that liberal prescription was justified. Of course, the analysis proved nothing of the sort, nor did it set out to. But the widely misread letter — now so well known it’s been nicknamed “Porter and Jick” — has been blamed for fueling the country’s opioid epidemic.

On Wednesday, the New England Journal of Medicine published a note from four Canadian researchers that shows the true scope of the letter’s influence, in what may be a first for the academic journal. The authors, led by Pamela T.M. Leung of the University of Toronto, found that “Porter and Jick” had been cited 608 times by other scholars — often inaccurately and uncritically.

Nearly 500 articles neglected to note that the letter concerned only hospitalized patients whose treatments were overseen by medical staff, rather than people prescribed take-home painkillers for, say, arthritis or minor injuries, the researchers found. A majority of the articles also cited the letter as evidence that addiction was rare in patients who took opioids. Other articles “grossly misrepresented” the letter’s findings, Leung and her team wrote.

“We believe that this citation pattern contributed to the North American opioid crisis by helping to shape a narrative that allayed prescribers’ concerns about the risk of addiction associated with long-term opioid therapy,” read the note which, like “Porter and Jick,” appeared in the journal’s letter to the editor section.

“The crisis arose in part because physicians were told that the risk of addiction was low when opioids were prescribed for chronic pain,” it read. “Our findings highlight the potential consequences of inaccurate citation and underscore the need for diligence when citing previously published studies.”

Some of the articles that cited “Porter and Jick” wildly inflated its conclusions, according to Leung and her team. “This pain population with no abuse history is literally at no risk for addiction,” read one article from 1998. “Medical opioid addiction is very rare,” read another from 2002.

If those claims sound ridiculous now, in 2017, it’s because they are. More than 183,000 people have died in the United States from prescription opioid overdoses since 1999, according to the Center for Disease Control and Prevention. Millions of other Americans struggle with painkiller addiction.

For Jick, who is still a drug specialist at Boston University School of Medicine, the letter was never intended to have any bearing on painkiller use outside short-term hospital visits.

“I’m essentially mortified that that letter to the editor was used as an excuse to do what these drug companies did,” he told the Associated Press on Wednesday. “They used this letter to spread the word that these drugs were not very addictive.”

An editor’s note on the New England Journal of Medicine now reads: “For reasons of public health, readers should be aware that this letter has been ‘heavily and uncritically cited’ as evidence that addiction is rare with opioid therapy.” It links to the review by the Canadian researchers.

The “Porter and Jick” letter as it appeared in the New England Journal of Medicine in 1980. (Screen grab)

The story behind the letter was documented extensively by journalist Sam Quinones in his 2015 book “Dreamland,” an account of the opioid crisis in the United States.

According to Quinones, the letter seemed to go largely unnoticed until 1986, when it was cited in a paper in Pain, the journal of the American Pain Society. From there, other scholars began to repeat its findings — often, as Quinones notes, without the important context that the patients analyzed were administered small doses of opioids by doctors, not sent home with bottles of prescription pills.

Eventually, the paragraph of findings became known simply as “Porter and Jick.” The nickname only made things worse.

“That shorthand, in turn, lent prestige to the tiny thing and the claim attributed to it: that less than 1 percent of patients treated with narcotics developed addictions to them,” Quinones writes.

By the 1990s, the letter had become a “foundation for a revolution in U.S. medical practice,” according to Dreamland. Researchers were urged to “consider the work” of Porter and Jick. A Scientific American article mentioned the pair’s “extensive study.” A registered nurse referred to it as “gospel.” And in 2001, Time magazine called it a “landmark study” showing that fears of addiction were “basically unwarranted.”

A key reason the letter was misinterpreted had to do with the New England Journal of Medicine’s archives, according to “Dreamland.” None of the journal’s material before 1993 was available online until 2010. So when the letter was cited, it had the appearance of being a peer-reviewed study, not a terse letter to the editor meant only to stimulate conversation among fellow researchers.

Jick went on to do a broad range of other scholarly work. And, as he told the Associated Press, he once testified as a witness for the government in a lawsuit involving the marketing of painkillers. He was apparently unaware for some time of what his short letter had triggered.

“It’s an amazing thing,” Jick said, according to “Dreamland.” “That particular letter, for me, is very near the bottom of a long lit of studies that I’ve done. It’s useful as it stands because there’s nothing else like it on hospitalized patients. But if you read it carefully, it does not speak to the level of addiction in outpatients who take these drugs for chronic pain.”